ESC Heart Failure最新文献

{"title":"Re-PERFUSE: Phase 1b study of AZD3427, a novel relaxin receptor agonist, on renal perfusion in HFrEF patients.","authors":"Marcin Ufnal, Macarena P Quintana-Hayashi, Kathleen Connolly, Daniel Pettersen, Zsolt Cselényi, Aurelija Jucaite, Magnus Schou, Andrea Varrone, Melanie Chan, Lars H Lund","doi":"10.1002/ehf2.15412","DOIUrl":"https://doi.org/10.1002/ehf2.15412","url":null,"abstract":"<p><strong>Aims: </strong>Renal impairment frequently coexists with heart failure (HF) and is associated with increased risk of poor clinical outcomes. This highlights the urgent need for therapies targeting both cardiac and renal dysfunction. AZD3427, a long-acting recombinant fusion protein and relaxin analogue that selectively activates the relaxin family peptide receptor 1 (RXFP1), showed trends of increased stroke volume and estimated glomerular filtration rate (eGFR) in HF patients (NCT04630067). The hypothesis is that AZD3427 may enhance GFR by expanding the functional renal cortex volume and improving renal perfusion.</p><p><strong>Methods and results: </strong>The Re-PERFUSE study (NCT06611423) is a Phase 1b, randomised, double-blind, placebo-controlled trial aimed at evaluating the effects of AZD3427 on renal perfusion in patients with HF and reduced ejection fraction (HFrEF) with reduced eGFR. Patients with HF, EF ≤ 40% and an eGFR of 30 to 90 mL/min/1.73 m², assessed by the CKD-EPI 2021, will receive a single dose of subcutaneous AZD3427 (n = 6) or placebo (n = 6). Intravenous dopamine will serve as a positive control for increased renal blood flow. Positron emission tomography (PET) imaging with [¹⁵O]-labelled water will be used to measure renal cortex blood flow pre- and post-treatment, allowing differentiation between global and focal renal blood flow changes and providing insights into potential nephron recruitment and increased filtration membrane area. Safety and tolerability will be assessed through monitoring of adverse events, clinical laboratory tests and vital signs.</p><p><strong>Conclusions: </strong>This study, alongside other ongoing AZD3427 studies, aims to evaluate the dual effects of AZD3427 in improving both cardiac and renal function. These insights could guide the development of future therapeutic strategies for managing HF and renal impairment.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic glycosyltransferase genes and potential therapeutic drugs in pressure overload-induced heart failure.","authors":"Jiahe Wu, Yi Lu, Xinchen Gao, Xiaorong Hu, Zhibing Lu, Chenze Li","doi":"10.1002/ehf2.15409","DOIUrl":"https://doi.org/10.1002/ehf2.15409","url":null,"abstract":"<p><strong>Aims: </strong>Protein glycosylation regulated by glycosyltransferases is an important type of post-translational modification. The role of the glycosyltransferase genes (GTGs) in heart failure (HF) remains unclear and requires further investigation.</p><p><strong>Methods: </strong>Differential expression analysis was performed on the transverse aortic constriction (TAC)-related dataset GSE36074 to screen out the differentially expressed GTGs. Enrichment and protein-protein interaction analyses explored their functional mechanisms and interconnections. Pearson correlation analysis revealed the relationship between GTGs and pathological cardiac remodelling. The upstream miRNAs of GTGs were predicted using corresponding online databases, and the downstream target genes were identified by weighted correlation network analysis (WGCNA). Computer virtual screening and molecular docking predicted potential therapeutic drugs. The identified GTGs were validated in vivo, in vitro and in the human HF-related dataset GSE57338.</p><p><strong>Results: </strong>Twenty-one differentially expressed GTGs were identified, and these genes were significantly up-regulated in the TAC model except for C1galt1, Extl2 and Pigh. Pearson correlation analysis revealed that 11 GTGs were significantly associated with pathological cardiac remodelling. Fifty-six miRNAs and 31 drugs were predicted to target these GTGs. WGCNA indicated that these GTGs were associated with lipid metabolism-related genes and pathways. Up-regulation of B3gnt9, C1galt1, Gcnt1, Gxylt2 and Mgat5b was observed in the TAC model. GXYLT2 is up-regulated and has high disease-predictive value in patients with dilated cardiomyopathy and ischaemic cardiomyopathy. Knockdown of GXYLT2 in human AC16 cardiomyocytes significantly attenuated angiotensin II (AngII)-induced hypertrophy.</p><p><strong>Conclusions: </strong>Dysregulation of GTG expression may affect TAC-induced HF through metabolic pathways, and GXYLT2 may be a new potential therapeutic target for HF.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac rehabilitation and health-related quality of life in preserved ejection fraction heart failure: A meta-analysis.","authors":"Chenyao Ding, Yawen Gao, Rod S Taylor","doi":"10.1002/ehf2.15404","DOIUrl":"10.1002/ehf2.15404","url":null,"abstract":"<p><strong>Aims: </strong>The study aims to evaluate the effects of exercise-based cardiac rehabilitation (ExCR) on the health-related quality of life (HRQoL) in people with heart failure preserved ejection fraction (HFpEF).</p><p><strong>Methods: </strong>This study is a systematic review and meta-analysis. Six bibliographic databases (Medline, Embase, Web of Science, Cumulative Index of Nursing and Allied Health Literature, Cochrane CENTRAL and China National Knowledge Infrastructure database) were searched to April 2024 for randomized controlled trials (RCTs), involving adults with HFpEF undertaking ExCR compared with no exercise control. Subgroup and sensitivity analyses were conducted to explore potential sources of statistical heterogeneity.</p><p><strong>Results: </strong>Twelve RCTs recruiting a total of 1005 HFpEF patients with a median of 16 weeks follow-up were included. Four trials defined HFpEF as an ejection fraction of ≥45% and eight trials as ≥50%. Compared with control, ExCR participation was associated with improvements in disease-specific HRQoL as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) [weighted mean difference (WMD): -6.72, 95% confidence interval (Cl): -12.00 to -1.44, P = 0.013] and Kansas City Cardiomyopathy Questionnaire (KCCQ) total scores (WMD: 5.34, 95% CI: 1.75 to 8.93, P < 0.0001) and generic HRQoL assessed by Short-Form 36 and EQ-5D. There was evidence (P ≤ 0.05) of greater improvements in MLHFQ total score with ExCR in trials with shorter exercise duration (<60 min/session), the presence of risk of bias, and larger sample size (>45 patients). Included trials were small and demonstrated substantial clinical and statistical heterogeneity with a range of: (1) population definitions (e.g., definition of HFpEF of ≥45% vs. ≥50%, level and nature of comorbidities), (2) ExCR interventions (e.g., exercise only vs. comprehensive CR programmes, different modes and intensity of exercise, centre- and home-based delivery) and (3) methods of HRQoL assessment (e.g., disease specific vs. generic measure).</p><p><strong>Conclusions: </strong>This meta-analysis of RCT evidence shows that participation in ExCR provides important gains in HRQoL of people with HFpEF. However, the results should be interpreted with caution given the substantial clinical and statistical heterogeneity. Well reported, fully powered RCTs with longer follow-up are needed to confirm these findings.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new staging system for hereditary transthyretin amyloidosis in the era of specific amyloidosis therapies.","authors":"Gabriela Neculae, Amira Zaroui, Robert Adam, Mounira Kharoubi, Benoit Funalot, Daniel Coriu, Ruxandra Jurcut, Thibaud Damy","doi":"10.1002/ehf2.15414","DOIUrl":"https://doi.org/10.1002/ehf2.15414","url":null,"abstract":"<p><strong>Objectives: </strong>Currently, there are two prognosis staging systems validated for transthyretin amyloidosis (ATTR). We sought to develop a new staging system dedicated to hereditary transthyretin amyloidosis (ATTRv) patients on specific treatments.</p><p><strong>Methods and results: </strong>A total of 258 patients diagnosed with ATTRv from two cardiac amyloidosis reference centres in France and Romania were stratified into three disease stages based on NT-proBNP, estimated glomerular filtration rate (eGFR) and global longitudinal strain (GLS). A staging system was created using the following criteria: GLS ≥ -11%, NT-proBNP ≥ 2000 ng/L and eGFR ≤ 65 mL/min. Stage I was defined as the presence of none of the criteria. Stage III was defined as GLS ≥ -11% and either one or both NT-proBNP and eGFR criteria, while the remaining patients were defined as Stage II. Stage I patients had a 98.5% (95% CI 94.8-100) 5-year survival rate, Stage II patients 75.1% (95% CI 64.8-87.1) and Stage III patients a 29.4% (95% CI 18.6-46.5) 5-year survival rate (Stage I vs. Stage II, P = 0.001; Stage II vs. Stage III, P < 0.001). After age is adjusted for, compared to Stage I, the hazard ratio (HR) for death was 9.9 (95% CI 1.28-76.27, P = 0.02) for Stage II and 39.75 (95% CI 5.28-299.54, P < 0.001) for Stage III patients. HRs and statistical significance were maintained across different ATTR genotypes. The staging system was validated in a cohort of 138 patients.</p><p><strong>Conclusions: </strong>We propose a novel staging system for ATTRv patients on specific treatment, based on two biological markers and one echocardiographic parameter, common in clinical practice.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pilot study on DNA methylation changes for non-invasive molecular diagnostics in heart failure.","authors":"Giuditta Benincasa, Francesco Cacciatore, Mark E Pepin, Francesco Curcio, Rosaria Chiappetti, Adam R Wende, Enrico Coscioni, Claudio Napoli","doi":"10.1002/ehf2.15402","DOIUrl":"10.1002/ehf2.15402","url":null,"abstract":"<p><strong>Aims: </strong>The current therapeutic approach to ischaemic (IsHF) and non-ischaemic (NIsHF) heart failure (HF) mainly overlooks the underlying aetiology owing to a lack knowledge of the differential molecular pathways that contribute to HF with reduced ejection fraction (HFrEF). Alterations in myocardial DNA methylation levels have been identified as potential biomarkers for HF irrespective of its aetiology. Due to the limited availability of cardiac tissues in clinics, our goal is to determine if DNA methylation changes in circulating CD4⁺ T lymphocytes, which are strongly involved in left ventricle remodelling, can help in differentiating IsHF and NIsHF causes among patients with HFrEF and if DNA methylation levels associate with key clinical features.</p><p><strong>Methods and results: </strong>We performed a post hoc network-oriented analysis of the original PRESMET clinical trial dataset (NCT05475028). Integrating epigenomic data obtained with the high-resolution reduced representation bisulfite sequencing (RRBS) platform and the left-ventricle interactome (protein-protein interaction map) we identified six differentially methylated CpG positions (DMPs), which were able to distinguish IsHF (n = 8) versus NIsHF (n = 4) patients with an area under the curve (AUC) > 0.8. Network-oriented DMPs were significantly hypomethylated in IsHF versus NIsHF and annotated to six genes, namely, cytoskeleton-associated protein 4 (CKAP4), carnitine palmitoyltransferase 1A (CPT1A), eukaryotic translation initiation factor 2 subunit beta (EIF2S2), spectrin beta (SPTB), synaptotagmin 6 (SYT6) and RAB11 family interacting protein 1 (RAB11FIP1) (P < 0.05). We found that the CD4⁺ T cell hypomethylation of EIF2S2 gene significantly correlated with VO₂ max (ρ = 0.73, P = 0.04), hypomethylation of RAB11FIP1 significantly correlated with MECKI score (ρ = -0.85, P = 0.001), whereas SPTB significantly correlated with VO₂ max (ρ = 0.73, P = 0.04), left ventricle mass index (ρ = -0.91, P = 0.005) and left ventricular ejection fraction (ρ = 0.83, P = 0.01) in IsHF patients.</p><p><strong>Conclusions: </strong>We demonstrate that circulating CD4⁺ T cell-specific methylation levels of network-oriented CKAP4, CPT1A, EIF2S2, SPTB, SYT6 and RAB11FIP1 genes can distinguish between IsHF and NIsHF. In particular, hypomethylation of EIF2S2, SPTB and RAB11FIP1 genes is significantly correlated with key clinical features in isHF patients, highlighting its potential to enhance personalized prognosis for HFrEF patients.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting acute decompensated heart failure using circadian markers from heart rate time series.","authors":"Valerie A A van Es, Mayke M C J van Leunen, Ignace L J de Lathauwer, Cindy C A G Verstappen, René A Tio, Ruud F Spee, Lu Yuan, Monica Betta, Giacomo Handjaras, Hareld M C Kemps","doi":"10.1002/ehf2.15395","DOIUrl":"https://doi.org/10.1002/ehf2.15395","url":null,"abstract":"<p><strong>Aims: </strong>Hospital admissions for acute decompensated heart failure (ADHF) are linked to high readmission rates, emphasizing the need for early intervention. Dysregulation of the circadian rhythm that regulates key physiological processes, such as heart rate (HR), blood pressure and sleep-wake cycles, may precede weight gain and clinical symptoms of worsening heart failure (HF) by weeks, providing a window for timely intervention. This study aims to develop a predictive algorithm for early and accurate ADHF detection.</p><p><strong>Methods and results: </strong>Sixty-five patients discharged after ADHF hospitalization monitored HR with a wrist-worn device for 6 months after reaching stable HF. Circadian parameters (mesor, amplitude and acrophase) were extracted via cosinor analysis and used to train a long short-term memory neural network. The algorithm analysed 21-day periods before an HF event, defined as unplanned outpatient visits for congestion episode, increased diuretics, ADHF hospitalization or sudden cardiac death. Circadian changes appeared in the 21 days preceding HF events, with elevated mesor (70.6 vs. 73.6 b.p.m.; P < 0.001), reduced amplitude (8.3 vs. 4.9 b.p.m.; P = 0.046) and acrophase shifts (11.3 vs. 12.2 h; P = 0.706). The classification algorithm showed 74% sensitivity, 73% specificity and a 74% AUC (P < 0.001). Amplitude was the strongest predictor, contributing 62% to the algorithm's feature importance.</p><p><strong>Conclusions: </strong>Circadian metrics from a wrist-worn device showed progressive alterations over the 3 weeks preceding ADHF, offering potential early detection of HF decompensation with moderate prediction performance. Future research should refine these metrics and results in larger, diverse populations, using various sensor types and explore early interventions.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prospective analysis of management and outcomes of worsening heart failure in the outpatient setting.","authors":"Joseph McCambridge, Fiyinfoluwa Fabamwo, Shadia Taha, Dermot McCaffrey, Matthew Barrett, Ciara Mahon, Kenneth McDonald","doi":"10.1002/ehf2.15400","DOIUrl":"https://doi.org/10.1002/ehf2.15400","url":null,"abstract":"<p><strong>Aims: </strong>There is growing recognition of the burden and prognostic significance of WHF treated in the outpatient setting. However, there is currently a lack of prospective real-world data in this area of HF care. This study aims to analyse the natural history of outpatient WHF.</p><p><strong>Methods and results: </strong>This is a prospective, observational study of consecutive patients treated for WHF in our ambulatory HF clinic from August 2022 to March 2024. The diagnosis of WHF was made according to two definitions. The first required meeting strict pre-specified diagnostic criteria. The second included patients not meeting these diagnostic criteria but deemed to have WHF by a senior cardiologist. All patients required escalation in diuretic therapy (oral and/or intravenous) for inclusion. Clinical endpoints included outcomes from the presenting WHF episode and over the subsequent 3 months. Of the 234 patients treated for outpatient WHF, stabilisation was achieved in 78.6% (184) with 16.2% (38) requiring HF hospitalisation. A further 3.4% (8) experienced non-HF-related admissions, 2 (0.9%) patients died without hospitalisation and 2 (0.9%) patients requested follow up in other units for geographic ease. Bailout therapies (oral metolazone and/or IV loop diuretic) were used in 45.3% (106), and adverse clinical outcomes were significantly higher in this group than among those treated with oral loop diuretic only (35.8%, 38/106 and 9.4%, 12/128 respectively; odds ratio 7.24, P < 0.001). Of those who initially stabilised, 24.5% (45/184) had recurrent outpatient WHF during the subsequent 3-month period of follow-up, and 4.9% (9/184) were hospitalised for HF.</p><p><strong>Conclusions: </strong>Outpatient WHF was successfully treated in the majority of patients in the community. However, despite initial stabilisation, there is a persistent risk of recurrent deterioration. This may reflect challenges in defining stability clinically in HF patients. Biologic markers of stability and closer follow-up may help to address this challenge and improve outlook for this at-risk group.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four decades of heart-lung transplantation: Milestones and outcomes in advanced cardiorespiratory failure.","authors":"L Lily Rosenthal, Anna Maria Mühlbauer, Carola Grinninger, Nikolaus A Haas, Heinrich Netz, Robert Dalla Pozza, Jürgen Hörer, Sebastian Michel, R Schramm, D Graetz, Christian Hagl","doi":"10.1002/ehf2.15411","DOIUrl":"https://doi.org/10.1002/ehf2.15411","url":null,"abstract":"<p><strong>Aims: </strong>Heart-lung transplantation (HLTx) remains a life-saving intervention for patients with end-stage cardiopulmonary failure. We retrospectively analysed long-term HLTx outcomes at our centre to assess survival trends and evaluate the impact of evolving immunosuppressive, surgical and perioperative strategies.</p><p><strong>Methods and results: </strong>This single-centre retrospective cohort study included 80 patients who underwent HLTx between 1983-1995 (Era 1) and 1996-2010 (Era 2), with follow-up through June 2024. All patients had severe cardiorespiratory failure. The primary endpoint was all-cause mortality. Secondary endpoints included early and late post-transplant outcomes. Overall survival at 1, 5 and 10 years post-transplant was 60 ± 6%, 46 ± 6% and 35 ± 6%, respectively. Survival improved significantly between Era 1 (46 ± 10%, 18 ± 9% and 9 ± 6%) and Era 2 (66 ± 7%, 5 ± 7% and 45 ± 7%) (P < 0.001), correlating with advancements in immunosuppression, organ preservation and perioperative care. Univariable risk factors for increased mortality included Euro Collins versus Perfadex lung preservation (P < 0.001), University of Wisconsin (UW2) versus Histidine-Tryptophan-Ketoglutarate (HTK) solution cardioplegia (P < 0.001), and Epstein-Barr virus infection (P = 0.036). Heart failure: OR 4.557 (95% CI: 1.057-19.648, P = 0.042) and gastrointestinal bleeding: OR 2.739 (95% CI: 1.310-5.726, P = 0.016) were identified as risks for mortality. These factors remained significant in multivariable analysis.</p><p><strong>Conclusions: </strong>HLTx outcomes at our centre are consistent with international benchmarks. Survival has improved in Era 2, likely due to individualised immunosuppressive regimens, novel organ preservation techniques and enhanced surveillance. These results support ongoing optimisation of multidisciplinary care for complex cardiopulmonary failure.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype characterization of heart failure with preserved ejection fraction in medical device and surgical trials.","authors":"Kurdo Araz, Francesco Fioretti, Sara Ladak, Mohammed Obaidan, Javed Butler, Aamir Hameed","doi":"10.1002/ehf2.15401","DOIUrl":"https://doi.org/10.1002/ehf2.15401","url":null,"abstract":"<p><strong>Aims: </strong>Heart failure with preserved ejection fraction (HFpEF) prevalence is nearing 50% of all heart failure cases and is often associated with advanced age, obesity, atrial fibrillation and hypertension, and medical approaches are limited. This review aims to determine the potential of medical devices or surgical interventions in treating HFpEF and to propose specific phenotypes of HFpEF.</p><p><strong>Methods and results: </strong>A systematic review was conducted using various clinical trial databases and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines followed by descriptive analysis and methodology quality assessment. Inclusion criteria included a medical device or surgical intervention involving HFpEF patients defined by a left ventricular ejection fraction (LVEF) ≥50% and signs of diastolic dysfunction. Twenty-four novel trials were identified involving n = 1752 participants: 17 medical device trials [3 interatrial shunt device trials (n = 1069), 1 atrial flow regulator trial (n = 41), 3 vagal nerve stimulation trials (n = 112), 1 baroreflex activation therapy trial (n = 21), 1 cardiac contractility modulator trial (n = 47), 6 cardiac resynchronization therapy trials (n = 178) and 2 functional electrical stimulation therapy trials (n = 89)] and 7 surgical intervention trials [1 renal denervation trial (n = 25), 3 greater splanchnic nerve ablation trials (n = 111), 2 catheter ablation trials (n = 55) and 1 pericardiotomy procedure trial (n = 4)]. One trial completed phase 3 trials, 20 trials completed phase 1 trials with further trials, and 5 trials completed phase 1 trials without further trials.</p><p><strong>Conclusions: </strong>Overall, 16 out of 24 trials have at least demonstrated safety and feasibility. However, despite many trials of a medical device or surgical procedure showing proof of concept to treat HFpEF phenotypes, they do not provide sufficient evidence of long-term benefit. More robust and phenotype-based clinical trials are needed to ensure evidence-based solutions are developed in HFpEF.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital implementation strategy to increase SGLT2 inhibitor uptake in heart failure: Study design of EMAIL-HF.","authors":"Mariam Elmegaard, Lars Køber, Mads Kristian Ersbøll, Theis Lange, Christian Ditlev Tuxen, Mette Rauhe Mouridsen, Trine Kiilerich Lauridsen, Jens Jakob Thune, Peter Godsk Jørgensen, Morten Lamberts, Nadia Paarup Dridi, Peter Bonfils, Morten Petersen, Nis Ottesen Stride, Anders Barasa, Jesper Jensen, Caroline Garred, Emil Fosbøl, Emil Wolsk, John McMurray, Mark Petrie, Morten Schou","doi":"10.1002/ehf2.15398","DOIUrl":"https://doi.org/10.1002/ehf2.15398","url":null,"abstract":"<p><strong>Aims: </strong>The EMAIL-HF trial aims to evaluate whether a digital guideline implementation strategy can increase and accelerate initiation of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with heart failure (HF).</p><p><strong>Methods and results: </strong>EMAIL-HF is a pragmatic, registry-based, randomized controlled trial including patients with a diagnosis of HF within the last 10 years, residing in the Capital Region of Denmark and the municipality of Roskilde (~2 million inhabitants). A total of 5996 eligible patients not already treated with SGLT2 inhibitors were identified from nationwide health registries and randomized 1:1 to either receive a digital letter providing information on SGLT2 inhibitors with an invitation for evaluation (intervention group: 2979 patients), or to usual care without the letter (control group: 3017 patients). The median age was 73 years (intervention) vs. 74 years (control), with 67.4% and 66.5% males, respectively. The primary outcome is the proportion of patients initiating SGLT2 inhibitor therapy within 6 months after randomization. The secondary outcome is a composite of time to first HF hospitalization or all-cause mortality. Additional exploratory outcomes include adherence, clinical events, healthcare utilization and subgroup analyses. Full baseline characteristics and clinical outcomes will be reported after completion of event accrual.</p><p><strong>Conclusions: </strong>EMAIL-HF will determine whether a population-wide digital strategy can increase and accelerate guideline-based initiation of SGLT2 inhibitors in patients with chronic HF. This trial may offer a scalable model to improve implementation of novel therapies in routine clinical practice.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}